Effect of Rivaroxaban vs Enoxaparin on Major Cardiac Adverse Events and Bleeding Risk in the Acute Phase of Acute Coronary Syndrome
Authors: Shenghua Zhou, Yichao Xiao, Chonglun Zhou, Zhaofen Zheng, Weihong Jiang, Qiang Shen, Can Zhu, Hongwei Pan, Changhui Liu, Gaofeng Zeng, Liangqing Ge, Yumin Zhang, Zewei Ouyang, Guang Fu, Gang Pan, Feng Chen, Lihong Huang, Qiming Liu, Xinqun Hu, Zhenfei Fang, Liang Tang, Xuping Li, Zhaowei Zhu, Shi Tai, Tao Tu, Hui Yang, Yuhu He, Mingxian Chen, Daoquan Peng, Yanshu Zhao, Danyan Xu, Jianjun Tang, Jiang Li, Yaqin Chen, Yi Li, Xiaolan Luo, Yong Huang, Jianqiang Xiang, Qinglin Guan, Xinyang Li, Xiaojun Yi, Fang Tan, Yan Liu, Jiang Pan, Jianqiang Peng, Sulan Yan, Zhengyu Liu, Bo Cui, Peng Wang, Yi Tang, Juan Wen, Hong Liu, Chunyan Weng, Xi Wu, Jingjia Yu, Qiong Yang, Liping Peng, Anying Li, Zhihui Zhang, Xiaowei Zhou, Huaqing Tan, Jie Chen, Zhiyuan Yang, Zhizhong Liang, Xiangyu Tang, Sha Chen, Lan Zeng, Yingtao Wu, Guangyao Chen, Dihua Yan, Lianghui Zhou, Siqin Yuan, Rong Wu, Pei Zhou, Yuzhen Fu, Youliang Huang, Wei Tang, Yang Nie, Hongju Xiang, Wei Chen, Zhiyong Yang, Yue Wu, Haishui Deng, Ming Lei, Bailing Zhang, Xing Xiang, Bingqing Xue, Liping Xiong, Xiping Xu, Xiaojian Feng, Jianhua Zhao, Yonghua Lu, Zhengzai Li, Bo Zhou, Cheng Li, Zibin Deng, Hongda Feng, Xibin Zhang, Guoli Wang, Zhi Chen, Wenxuan Zeng, Di Shen, Xiangyong Hu, Xuemei Chen, Zuoan Qin, Sulan Huang, Ning Guo, Zhixiang Zhang, Kun Chen, Bingxing Gong, Min Yin, Tao Qin, Tao Hu, Jiangbiao Yu, Ting Zhang, Xingcheng Guo, Hui Peng, Minming Yin, Huaineng Zhou, Li Luo, Xiaoxia Xiao, Yong Quan, Weifen Liang, Yang Wu, Hang Chen, Wei Shi, Aiying Liu, Yijian Liu, Guiyun Ruan, Peng Liu, Canxiang Luo, Lin He, Li Deng, Shayan Sun, Shuo Yang, Sha Wang, Songbing Long, Yizhu Duan, Jin Luo, Zhengjie Xue, Luzhu Chen, Caiyan Guo, Yongjun Yin, Yanbo Wang, Fan Ouyang, Shuhong Guo, Weiqing Liu, Chunfeng Liao, Dongsheng Lin, Huijuan Chen, Lixia Ma, Hui Luo, Jianfeng Wu, Chao Yang, Yang Liu, Yingnan Qin, Fangyao Liu, Jianqiang Xu, Juan Tang, Yixin Tang, Hengjing Hu, Jiming Zhou, Jingyong Yang, Tingting Deng, Ping Xiao, Jun Liu, Shenyi Guo, Wenjie Liu, Xing Zhang, Zhihong Li, Renhua Zeng, Zhen Zhou, Jianhong Bao, Ye Zhou, Xiaojuan Wang, He Huang, Yunlong Zhu, Wenjiao Zhao, Xianming Wu, Ming Cai, Fan Liu, Luping Jiang, Zehua Li, Songquan Peng, Qiao Jin, Chun Chen, Lu Hu, Ting Zhou, Pengcui Wu, Xiao Long, Yuyan Huang, Hebin Xie, Tao Yang, Shao Ouyang, Xiang Liu, Song Hu, Zhenhua Xing, Jianping Zeng, Yi Zhang
Journal: JAMA Network Open (2023)

Importance Parenteral enoxaparin is a preferred anticoagulant used in the acute phase for patients with acute coronary syndrome (ACS). The safety and efficacy of short-term low-dose rivaroxaban in this clinical setting remain unknown. Objective To compare the safety and efficacy of rivaroxaban vs enoxaparin in the acute phase of ACS. Design, Setting, and Participants This multicenter, prospective, open-label, active-controlled, equivalence and noninferiority trial was conducted from January 2017 through May 2021 with a 6-month follow-up at 21 hospitals in China. Participants included patients with ACS missing the primary reperfusion window or before selective revascularization. Data were analyzed from November 2021 to November 2022. Interventions Participants were randomized 1:1:1 to oral rivaroxaban 2.5 mg or 5 mg or 1 mg/kg subcutaneous enoxaparin twice daily in addition to dual antiplatelet therapy (DAPT; aspirin 100 mg and clopidogrel 75 mg once daily) for a mean of 3.7 days. Main Outcomes and Measures The primary safety end point was bleeding events, as defined by the International Society on Thrombosis and Haemostasis, and the primary efficacy end point was major adverse cardiovascular events (MACEs), including cardiac death, myocardial infarction, rerevascularization, or stroke during the 6-month follow-up. Results Of 2055 enrolled patients, 2046 (99.6%) completed the trial (mean [SD] age 65.8 [8.2] years, 1443 [70.5%] male) and were randomized to enoxaparin (680 patients), rivaroxaban 2.5 mg (683 patients), or rivaroxaban 5 mg (683 patients). Bleeding rates were 46 patients (6.8%) in the enoxaparin group, 32 patients (4.7%) in the rivaroxaban 2.5 mg group, and 36 patients (5.3%)in the rivaroxaban 5 mg group (rivaroxaban 2.5 mg vs enoxaparin: noninferiority hazard ratio [HR], 0.68; 95% CI, 0.43 to 1.07; P = .005; rivaroxaban 5 mg vs enoxaparin: noninferiority HR, 0.88; 95% CI, 0.70 to 1.09; P = .001). The incidence of MACEs was similar among groups, and noninferiority was reached in the rivaroxaban 5 mg group (HR, 0.60; 95% CI, 0.31 to 1.16, P = .02) but not in the rivaroxaban 2.5 mg group (HR, 0.68; 95% CI, 0.36 to 1.30; P = .05) compared with the enoxaparin group. Conclusions and Relevance In this equivalence and noninferiority trial, oral rivaroxaban 5 mg showed noninferiority to subcutaneous enoxaparin (1 mg/kg) for patients with ACS treated with DAPT during the acute phase. Results of this feasibility study provide useful information for designing future randomized clinical trials with sufficient sample sizes. Trial Registration ClinicalTrials.gov Identifier: NCT03363035